OVARIAN HORMONE-INDUCED BETA-CELL HYPERTROPHY CONTRIBUTES TO THE HOMEOSTATIC CONTROL OF BETA-CELL MASS IN OLETF FEMALE RAT, A MODEL OF TYPE-II DIABETES

A sexual dimorphism regarding the incidence of diabetes mellitus in OL ETF rat, a model of Type II diabetes, has been reported. As a result, the effects of ovarian hormones on beta cells per se was examined by c omparing the capacity of beta-cell proliferation and changes in blood glucose and plasma insulin concentrations after a 70 % pancreatectomy. All female animals were randomly assigned to two protocols. The rats involved in protocol I received either a 70 % pancreatectomy (Px) or a sham pancreatectomy (sham) at 6 weeks of age, along with their diabet es-resistant counterparts, female LETO rats, which served as normal co ntrols. The rats belonging to protocol II were given an ovariectomy (O x) at 5 weeks of age, and one week later, they were subjected to eithe r Pr or the sham operation, with/without hormone (estradiol, 50 mu g/k g; testosterone, 1 mg/kg) replacement. The findings indicate that the capacity for compensatory growth of beta cells after Pr was affected b y both sex hormonal and genetic components, since a 70% Pr resulted in sustained hyperglycaemia within the first week after surgery, but was ameliorated by an increase in beta-cell mass thereafter in the non-Ox Pr OLETF rats. The Ox also caused a decline in beta-cell mass which c ould be improved by replacement with ovarian hormones. Not only endoge nous but also replacement ovarian hormones, led to a beneficial effect on beta cells per se in OLETF female rats. This was reflected by an i ncreased beta-cell mass accompanied by a parallel increase in plasma i mmunoreactive insulin concentration. The effects of ovarian hormones, however, contributed to the beta-cell hypertrophy rather than expansio n of the beta-cell population to achieve glucose homeostasis, as evide nced by an increased area of individual beta-cell after Px rather than an increased BrdU-labelling index for the beta cells. The present stu dy suggests that ovarian hormone-induced beta-cell hypertrophy may typ ically occur: to compensate for changes in functional demand as the re sults of a 70 % Pr in female OLETF rats.